P. Gerwins et al., Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis, CR R ONC H, 34(3), 2000, pp. 185-194
Angiogenesis, formation of new vessels from pre-existing ones, results from
stimulation of endothelial cells, which line the vessel wall. These cells
will leave their resting state and start to digest the basement membrane, p
roliferate, migrate and eventually differentiate to form a hollow tube. All
these steps can be induced by growth factors and this review will focus on
two important types of angiogenic growth factors, vascular endothelial gro
wth factor (VEGF; also denoted vascular permeability factor, VPF) and fibro
blast growth factor (FGF). Both types of factors bind to cell surface expre
ssed receptors, which are ligand-stimulatable tyrosine kinases. Binding of
the growth factors to their receptors leads to activation of the intrinsic
tyrosine kinase and signal transduction to downstream signalling cascades.
This results in transcriptional changes and biological responses. The molec
ular aspects of signalling cascades critical for endothelial cell prolifera
tion and migration are beginning to be delineated. In contrast, signalling
cascades leading to endothelial cell differentiation remain to be determine
d. Angiogenesis is essential for a number of physiological events such as e
mbryonic development, ovulation, and wound healing. It has become increasin
gly clear that a number of diseases depend on angiogenesis. For future deve
lopment of therapeutic tools, it is important to understand the molecular m
echanisms that regulate angiogenesis. (C) 2000 Elsevier Science Ireland Ltd
. All rights reserved.